4-Fluoro-2-trifluoromethylbenzonitrile

Base Information

• Chemical Name: 4-Fluoro-2-trifluoromethylbenzonitrile
• CAS No.: 194853-86-6
• Molecular Formula: C8H3F4N
• Molecular Weight: 189.112
• Hs Code.: 29269090
• Mol file: 194853-86-6.mol

Synonyms:2-Trifluoromethyl-4-fluorobenzonitrile;4-Fluoro-2-(trifluoromethyl)benzonitrile;

Chemical Property of 4-Fluoro-2-trifluoromethylbenzonitrile

Chemical Property:

• Appearance/Colour: white or off white crystalline
• Vapor Pressure: 0.269mmHg at 25°C
• Melting Point: 43-45 °C
• Refractive Index: 1.443
• Boiling Point: 204.1 °C at 760 mmHg
• Flash Point: 98.4 °C
• PSA: 23.79000
• Density: 1.37 g/cm³
• LogP: 2.71618
• Storage Temp.: Sealed in dry,Room Temperature
• Solubility.: Chloroform (Sparingly), Methanol (Slightly)
• Water Solubility.: Insoluble in water. Solubility in methanol is almost transparent.

Purity/Quality:

99% ^*data from raw suppliers

4-Fluoro-2-(trifluoromethyl)benzonitrile ^*data from reagent suppliers

Safty Information:

• Pictogram(s): Xi,T,Xn
• Hazard Codes: T,Xi,Xn
• Statements: 20/21/22-36/37/38-22
• Safety Statements: 26-36/37/39-45-36-36/37-23-9

MSDS Files:

SDS file from LookChem

Useful:

• Uses: It is used as a pharmaceutical intermediate. It is also used for the synthesis of diphenylthioethers.

Technology Process of 4-Fluoro-2-trifluoromethylbenzonitrile

There total 2 articles about 4-Fluoro-2-trifluoromethylbenzonitrile which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 96.0%

[(4-chlorophenyl)thio]pentafluorobenzene (16495-77-5) + C15H7F3N2O → 1-[(4-chlorophenyl)thio]-4-[(4-cyanophenyl)oxy]-2,3,5,6-tetrafluorobenzene + 4-fluoro-2-(trifluoromethyl)benzonitrile (194853-86-6)

Guidance literature:

With bis[1,2-bis(diphenylphosphino)benzene]hydriderhodium(I); In chlorobenzene; for 3h; Inert atmosphere; Reflux;

DOI:10.1039/c6cc05400e

Reference yield:

4-fluorobenzonitrile (1194-02-1,143234-87-1) + trifluoroacetic acid (76-05-1) → 4-Fluoro-3-(trifluoromethyl)benzonitrile (67515-59-7) + 4-fluoro-2-(trifluoromethyl)benzonitrile (194853-86-6)

Guidance literature:

With dipotassium peroxodisulfate; sulfuric acid; sodium carbonate; silver carbonate; In dichloromethane; at 120 ℃; for 10h; Schlenk technique; Sealed tube;

DOI:10.1021/ol503189j

Reference yield: 100.0%

D-allo-threonine (24830-94-2,134357-96-3,7013-32-3,82822-12-6) + 4-fluoro-2-(trifluoromethyl)benzonitrile (194853-86-6) → (2R,3R)-2-(4-cyano-3-(trifluoromethyl)phenylamino)-3-hydroxybutanoic acid (1182368-21-3)

Guidance literature:

D-allo-threonine; 4-fluoro-2-(trifluoromethyl)benzonitrile; With potassium carbonate; In dimethyl sulfoxide; at 20 - 75 ℃;

With citric acid; In water;

upstream raw materials:

4-fluorobenzonitrile

trifluoroacetic acid

[(4-chlorophenyl)thio]pentafluorobenzene

Downstream raw materials:

4-(4-chloro-2-methyl-quinolin-7-ylmethoxy)-2-trifluoromethyl-benzonitrile

4-(4,4-dimethyl-2,5-dioxoimidazolidin-1-yl)-2-(trifluoromethyl)benzonitrile

N-[4-cyano-3-(trifluoromethyl)phenyl]-2-methylacrylamide

4-(piperazin-1-yl)-2-(trifluoromethyl)benzonitrile

Refernces

Rational design and synthesis of 4-((1R,2R)-2-hydroxycyclohexyl)- 2(trifluoromethyl)benzonitrile (PF-998425), a novel, nonsteroidal androgen receptor antagonist devoid of phototoxicity for dermatological indications

10.1021/jm8009316

The research details the rational design and synthesis of a novel nonsteroidal androgen receptor antagonist, PF-998425, intended for dermatological applications such as sebum control and treatment of androgenetic alopecia. The compound was designed to be potent, selective, and devoid of phototoxicity, a common issue with similar drugs. The study involved high-throughput screening using a [3H]DHT competitive ligand binding assay and MDA-MB-453-MMTV-luci cell line to identify active compounds. The synthesis of PF-998425 included a series of chemical reactions starting from 4-fluoro-2-(trifluoromethyl)benzonitrile and cyclohexanone, leading to the desired cis-alcohol (-)-6a with a key step being an asymmetric epoxidation using Jacobsen’s (S,S)Mn(III)-salen complex catalyst. The compound's activity was confirmed through in vitro assays, including binding assays and cellular functional assays, with IC50 values indicating potency. The compound's selectivity was tested against other nuclear hormone receptors, and its pharmacokinetics, in vivo activity, and safety were evaluated using various models and assays, including the 3T3 neutral red uptake (NRU) phototoxicity test, metabolic stability in rat liver microsomes, and pharmacokinetics in dogs. The results showed that PF-998425 was active in reducing sebum and stimulating hair growth without causing phototoxicity or significant systemic side effects, making it a promising candidate for topical dermatological treatments.